Tags

Type your tag names separated by a space and hit enter

Langerhans cells are critical in the development of atopic dermatitis-like inflammation and symptoms in mice.
J Cell Mol Med. 2009 Aug; 13(8B):2658-72.JC

Abstract

Genetic or vitamin D3-induced overexpression of thymic stromal lymphopoietin (TSLP) by keratinocytes results in an atopic dermatitis (AD)-like inflammatory phenotype in mice echoing the discovery of high TSLP expression in epidermis from AD patients. Although skin dendritic cells (DC) are suspected to be involved in AD, direct evidence of a pathogenetic role for skin DC in TSLP-induced skin inflammation has not yet been demonstrated. In a mouse model of AD, i.e. mice treated with the low-calcemic vitamin D3 analogue, MC903, we show that epidermal Langerhans cells (LC)-depleted mice treated with MC903 do neither develop AD-like inflammation nor increased serum IgE as compared to vitamin D3 analogue-treated control mice. Accordingly, we show that, in mice treated with MC903 or in K14-TSLP transgenic mice, expression of maturation markers by LC is increased whereas maturation of dermal DC is not altered. Moreover, only LC are responsible for the polarization of naïve CD4(+) T cells to a Th2 phenotype, i.e. decrease in interferon-gamma and increase in interleukin (IL)-13 production by CD4(+) T cells. This effect of LC on T-lymphocytes does not require OX40-L/CD134 and is mediated by a concomitant down-regulation of IL-12 and CD70. Although it was previously stated that TSLP up-regulates the production of thymus and activation-regulated chemokine (TARC)/chemokine (C-C motif) ligand 17 (CCL17) and macrophage-derived chemokine (MDC)/CCL22 by human LC in vitro, our work shows that production of these Th2- cell attracting chemokines is increased only in keratinocytes in response to TSLP overexpression. These results demonstrate that LC are required for the development of AD in mouse models of AD involving epidermal TSLP overexpression.

Authors+Show Affiliations

Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19538461

Citation

Elentner, Andreas, et al. "Langerhans Cells Are Critical in the Development of Atopic Dermatitis-like Inflammation and Symptoms in Mice." Journal of Cellular and Molecular Medicine, vol. 13, no. 8B, 2009, pp. 2658-72.
Elentner A, Finke D, Schmuth M, et al. Langerhans cells are critical in the development of atopic dermatitis-like inflammation and symptoms in mice. J Cell Mol Med. 2009;13(8B):2658-72.
Elentner, A., Finke, D., Schmuth, M., Chappaz, S., Ebner, S., Malissen, B., Kissenpfennig, A., Romani, N., & Dubrac, S. (2009). Langerhans cells are critical in the development of atopic dermatitis-like inflammation and symptoms in mice. Journal of Cellular and Molecular Medicine, 13(8B), 2658-72. https://doi.org/10.1111/j.1582-4934.2009.00797.x
Elentner A, et al. Langerhans Cells Are Critical in the Development of Atopic Dermatitis-like Inflammation and Symptoms in Mice. J Cell Mol Med. 2009;13(8B):2658-72. PubMed PMID: 19538461.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Langerhans cells are critical in the development of atopic dermatitis-like inflammation and symptoms in mice. AU - Elentner,Andreas, AU - Finke,Daniela, AU - Schmuth,Matthias, AU - Chappaz,Stéphane, AU - Ebner,Susanne, AU - Malissen,Bernard, AU - Kissenpfennig,Adrien, AU - Romani,Nikolaus, AU - Dubrac,Sandrine, Y1 - 2009/06/16/ PY - 2009/6/23/entrez PY - 2009/6/23/pubmed PY - 2010/7/20/medline SP - 2658 EP - 72 JF - Journal of cellular and molecular medicine JO - J. Cell. Mol. Med. VL - 13 IS - 8B N2 - Genetic or vitamin D3-induced overexpression of thymic stromal lymphopoietin (TSLP) by keratinocytes results in an atopic dermatitis (AD)-like inflammatory phenotype in mice echoing the discovery of high TSLP expression in epidermis from AD patients. Although skin dendritic cells (DC) are suspected to be involved in AD, direct evidence of a pathogenetic role for skin DC in TSLP-induced skin inflammation has not yet been demonstrated. In a mouse model of AD, i.e. mice treated with the low-calcemic vitamin D3 analogue, MC903, we show that epidermal Langerhans cells (LC)-depleted mice treated with MC903 do neither develop AD-like inflammation nor increased serum IgE as compared to vitamin D3 analogue-treated control mice. Accordingly, we show that, in mice treated with MC903 or in K14-TSLP transgenic mice, expression of maturation markers by LC is increased whereas maturation of dermal DC is not altered. Moreover, only LC are responsible for the polarization of naïve CD4(+) T cells to a Th2 phenotype, i.e. decrease in interferon-gamma and increase in interleukin (IL)-13 production by CD4(+) T cells. This effect of LC on T-lymphocytes does not require OX40-L/CD134 and is mediated by a concomitant down-regulation of IL-12 and CD70. Although it was previously stated that TSLP up-regulates the production of thymus and activation-regulated chemokine (TARC)/chemokine (C-C motif) ligand 17 (CCL17) and macrophage-derived chemokine (MDC)/CCL22 by human LC in vitro, our work shows that production of these Th2- cell attracting chemokines is increased only in keratinocytes in response to TSLP overexpression. These results demonstrate that LC are required for the development of AD in mouse models of AD involving epidermal TSLP overexpression. SN - 1582-4934 UR - https://www.unboundmedicine.com/medline/citation/19538461/Langerhans_cells_are_critical_in_the_development_of_atopic_dermatitis_like_inflammation_and_symptoms_in_mice_ L2 - https://doi.org/10.1111/j.1582-4934.2009.00797.x DB - PRIME DP - Unbound Medicine ER -